A5102742935- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Advanced Causal Inference Techniques
- Photoreceptor and optogenetics research
- Health disparities and outcomes
- Health Systems, Economic Evaluations, Quality of Life
- Retinal and Optic Conditions
- Genetic Associations and Epidemiology
- Statistical Methods in Clinical Trials
- Retinopathy of Prematurity Studies
- RNA regulation and disease
- Mental Health Treatment and Access
- Mental Health Research Topics
- Glaucoma and retinal disorders
- Child and Adolescent Psychosocial and Emotional Development
- Health, Environment, Cognitive Aging
- Cognitive Abilities and Testing
- Cellular transport and secretion
- Food Security and Health in Diverse Populations
- Schizophrenia research and treatment
- Retinal and Macular Surgery
- Lymphoma Diagnosis and Treatment
- Racial and Ethnic Identity Research
- Ophthalmology and Visual Impairment Studies
- Resilience and Mental Health
Columbia University
2009-2025
University of California, Santa Cruz
2024
Carmel Medical Center
2022
Penn Presbyterian Medical Center
2009-2018
University of Pennsylvania
2009-2018
Pfizer (United States)
2011-2014
Jefferson College
2014
École des Hautes Études en Santé Publique
2011
University of Liège
2009
University of Florida
2009
Are inverse relations between psychiatric disorders and socioeconomic status due more to social causation (adversity stress) or selection (downward mobility of genetically predisposed)? This classical epidemiological issue is tested by focusing on ethnic in relation status. Ethnic cannot be an effect disorder because it present at birth whereas depends educational occupational attainment. A cohort sample 4914 young, Israel-born adults European North African background was selected from the...
Leber congenital amaurosis (LCA) is a group of autosomal recessive blinding retinal diseases that are incurable. One molecular form caused by mutations in the RPE65 (retinal pigment epithelium-specific 65-kDa) gene. A recombinant adeno-associated virus serotype 2 (rAAV2) vector, altered to carry human gene (rAAV2-CBSB-hRPE65), restored vision animal models with deficiency. clinical trial was designed assess safety rAAV2-CBSB-hRPE65 subjects RPE65-LCA. Three young adults (ages 21–24 years)...
Ecological studies have been evaluated in epidemiological contexts terms of the "ecological fallacy." Although empirical evidence for a lack comparability between correlations derived from ecological- and individual-level analyses is compelling, conceptual meaning ecological fallacy remains problematic. This paper argues that issues cross-level inference can be usefully conceptualized as validity problems, problems not peculiar to ecological-level analyses. Such an approach increases...
The RPE65 gene encodes the isomerase of retinoid cycle, enzymatic pathway that underlies mammalian vision. Mutations in disrupt cycle and cause a congenital human blindness known as Leber amaurosis (LCA). We used adeno-associated virus-2-based replacement therapy to treat three young adults with RPE65-LCA measured their vision before up 90 days after intervention. All patients showed statistically significant increase visual sensitivity at 30 treatment localized retinal areas had received...
Significance The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. disease component not studied, however, been the fate of photoreceptors this progressive degeneration. We show that improves vision for at least 3 y, but photoreceptor degeneration progresses unabated humans. In canine model, same result occurs when treatment is stage equivalent to study shows need combinatorial improve short term also slow long term.
Retinal gene therapy for Leber's congenital amaurosis, an autosomal recessive childhood blindness, has been widely considered to be safe and efficacious. Three years after therapy, improvement in vision was maintained, but the rate of loss photoreceptors treated retina same as that untreated retina. Here we describe long-term follow-up data from three patients. Topographic maps visual sensitivity regions, nearly 6 two patients 4.5 third patient, indicate progressive diminution areas improved...
Human gene therapy with rAAV2-vector was performed for the RPE65 form of childhood blindness called Leber congenital amaurosis. In three contemporaneous studies by independent groups, procedure deemed safe and there evidence visual gain in short term. At 12 months after treatment, our young adult subjects remained healthy without vector-related serious adverse events. Results immunological assays to identify reaction AAV serotype 2 capsid were unchanged from baseline measurements. clinical...
This article reports a study of the function and composition social support networks among diverse lesbian, gay, bisexual (LGB) men women (n = 396) in comparison to their heterosexual peers 128). Data were collected using structured network matrix community sample recruited New York City. Our findings show that gay may rely on "chosen families" more than lesbian women. Both heterosexuals LGBs relied less family other people (e.g., friends, coworkers) for everyday recreational activities,...
Past studies have reported little about variability in mental disorders among lesbians, gay men, and bisexual individuals. We assessed the prevalence of psychiatric 388 lesbian, gay, Black, Latino, White Black individuals had lower all than did Latino individuals; younger cohorts fewer mood older cohorts; persons more substance use men lesbians; respondents attempted suicide often respondents.
Mutations in RPE65, a gene essential to normal operation of the visual (retinoid) cycle, cause childhood blindness known as Leber congenital amaurosis (LCA). Retinal therapy restores vision blind canine and murine models LCA. Gene humans with LCA from RPE65 mutations may also have potential for success but only if retinal photoreceptor layer is intact, early-disease stage-treated animals. Here, we use high-resolution vivo microscopy quantify thickness human disease define relationship...
Mutations in ABCA4, which encodes a photoreceptor specific ATP-binding cassette transporter (ABCR), cause autosomal recessive forms of human blindness due to retinal degeneration (RD) including Stargardt disease. The exact disease sequence leading and vision loss ABCA4-RD is not known. Extrapolation from murine vitro studies predicts that two the earliest pathophysiological features resulting disturbed ABCR function man would be slowed kinetics retinoid cycle accelerated deposition...
OBJECTIVES: This study examined the impact of assessing causes interindividual variation within a population when research question interest is about differences between populations or time periods. discrepancy focus and referred to as type III error, one that provides right answer for wrong question. METHODS: Homelessness, obesity, infant mortality were used illustrate different consequences errors. These depend on relationships within- between-group variation. CONCLUSIONS: The...
Recent criticism of epidemiologic methods has focused on the limitations 'black box' epidemiology, a pejorative label given to simple identification exposure–disease relationships. The assessment mediation is an important tool for addressing this criticism. By using analysis open black box, underlying mechanisms observed associations can be described and causal inference improved. An explicit theoretical motivation such been missing from epidemiological literature. To provide motivation, we...
AAV2 delivery of the RPE65 gene to retina blind RPE65-deficient animals restores vision. This strategy is being considered for human trials in RPE65-associated Leber congenital amaurosis (LCA), but toxicity and dose efficacy have not been defined. We studied ocular AAV-2/2.RPE65 RPE65-mutant dogs. There was no systemic toxicity. Ocular examinations showed mild or moderate inflammation that resolved over 3 months. Retinal histopathology indicated traumatic lesions from injection were common,...
Autosomal recessive retinal diseases caused by mutations in the ABCA4 gene are being considered for replacement therapy. All individuals with ABCA4-disease show macular degeneration, but only some thought to progress retina-wide blindness. It is currently not predictable if or when specific genotypes will extramacular disease, and how fast it thereafter. Early clinical trials of focal subretinal therapy aim arrest disease progression retina. In 66 known disease-causing alleles, we defined...
purpose. To characterize in detail the disease expression choroideremia (CHM), a blinding X-linked of retina caused by loss-of-function mutations Rab Escort Protein 1 (REP-1). CHM is readily diagnosed clinic and molecular testing but has lacked an animal model to test hypotheses therapeutics. The recent report mouse for prompts need reassessment human anticipation treatment initiatives. methods. hemizygotes with REP-1 mutations, spanning age range 7 decades, were studied vivo microscopy...
Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with Joubert syndrome and most common cause of childhood recessive blindness known as Leber congenital amaurosis (LCA). An in-frame deletion Cep290 shows rapid degeneration rod-rich mouse retina. To explore mechanisms human retinal disease, we studied CEP290-LCA patients different ages (7–48 years) compared results to Cep290-mutant mice. Unexpectedly, blind CEP290-mutant retinas retained photoreceptor inner laminar...
The visual (retinoid) cycle, the enzymatic pathway that regenerates chromophore after light absorption, is located primarily in retinal pigment epithelium (RPE) and essential for rod photoreceptor survival. Whether this also cone survival unknown, there are no data from man or monkey to address question. cycle naturally disrupted humans with Leber congenital amaurosis (LCA), which caused by mutations RPE65, gene encodes retinoid isomerase. We investigated such patients over a wide age range...
Leber congenital amaurosis (LCA), a severe autosomal recessive childhood blindness, is caused by mutations in at least 15 genes. The most common molecular form ciliopathy due to NPHP6 (CEP290) and subjects have profound loss of vision. A similarly phenotype occurs the related NPHP5 (IQCB1)-LCA. Recent success retinal gene therapy one LCA prompted question whether we know enough about human disease plan such treatment. We determined that there was early-onset rapid degeneration rod...